Normal immune response to microbial pathogens generates inflammation, which is essential for the clearance of the pathogen. First responders are innate cells that develop with the capacity to respond rapidly often by producing large amounts of cytokines. One important category of early responders are invariant natural killer T (iNKT) cells. These cells have a very restricted T cell receptor (TCR) repertoire and express several cell surface markers in common with natural killer cells. iNKT cells develop in the thymus and in the absence of encounter with any pathogen acquire the ability to rapidly produce cytokines. iNKT cells co-express co-factor CD4 or are CD4- and CD8-. Recently, a novel CD8 expressing innate T cells was described that they develop in the thymus have an unrestricted TCR repertoire and acquire the capacity to rapidly produce interferon gamma in response to TCR stimulation. Long term goals of this project are to define how the innate immune system changes with age and understand the molecular basis for the failure to adequately respond to invading pathogens. These studies might also provide insight into the decreased capacity of older individuals to respond to immunization.